Cargando…

CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)

Dysregulation of interleukin‐33 (IL‐33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the...

Descripción completa

Detalles Bibliográficos
Autores principales: Larsen, Sylvester, Seidelin, Jakob Benedict, Davidsen, Johanne, Dahlgaard, Katja, Nielsen, Claus Henrik, Bennett, Eric Paul, Pedersen, Ole Birger, Coskun, Mehmet, Troelsen, Jesper Thorvald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167865/
https://www.ncbi.nlm.nih.gov/pubmed/33838073
http://dx.doi.org/10.1002/2211-5463.13161
_version_ 1783701777655267328
author Larsen, Sylvester
Seidelin, Jakob Benedict
Davidsen, Johanne
Dahlgaard, Katja
Nielsen, Claus Henrik
Bennett, Eric Paul
Pedersen, Ole Birger
Coskun, Mehmet
Troelsen, Jesper Thorvald
author_facet Larsen, Sylvester
Seidelin, Jakob Benedict
Davidsen, Johanne
Dahlgaard, Katja
Nielsen, Claus Henrik
Bennett, Eric Paul
Pedersen, Ole Birger
Coskun, Mehmet
Troelsen, Jesper Thorvald
author_sort Larsen, Sylvester
collection PubMed
description Dysregulation of interleukin‐33 (IL‐33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the intestinal‐specific transcription factor CDX2 is a key component. In this study, we investigated whether CDX2 regulates IL33 mRNA expression. We examined IL33 mRNA expression in primary colonic epithelial cells from healthy humans and epithelial cell lines, revealing high expression levels in primary colonic and LS174T cells. Combining genomics data (ChIP‐seq, RNA‐seq) and IL33 promoter analyses in LS174T cells revealed intronic enhancer activity in the IL33 gene that is dependent on CDX2 expression. Western blotting and qRT‐PCR confirmed that IL33 expression is upregulated in a CDX2 concentration‐dependent manner, thereby providing the first evidence that CDX2 regulates the expression of IL33.
format Online
Article
Text
id pubmed-8167865
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-81678652021-06-05 CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T) Larsen, Sylvester Seidelin, Jakob Benedict Davidsen, Johanne Dahlgaard, Katja Nielsen, Claus Henrik Bennett, Eric Paul Pedersen, Ole Birger Coskun, Mehmet Troelsen, Jesper Thorvald FEBS Open Bio Research Articles Dysregulation of interleukin‐33 (IL‐33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the intestinal‐specific transcription factor CDX2 is a key component. In this study, we investigated whether CDX2 regulates IL33 mRNA expression. We examined IL33 mRNA expression in primary colonic epithelial cells from healthy humans and epithelial cell lines, revealing high expression levels in primary colonic and LS174T cells. Combining genomics data (ChIP‐seq, RNA‐seq) and IL33 promoter analyses in LS174T cells revealed intronic enhancer activity in the IL33 gene that is dependent on CDX2 expression. Western blotting and qRT‐PCR confirmed that IL33 expression is upregulated in a CDX2 concentration‐dependent manner, thereby providing the first evidence that CDX2 regulates the expression of IL33. John Wiley and Sons Inc. 2021-05-02 /pmc/articles/PMC8167865/ /pubmed/33838073 http://dx.doi.org/10.1002/2211-5463.13161 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Larsen, Sylvester
Seidelin, Jakob Benedict
Davidsen, Johanne
Dahlgaard, Katja
Nielsen, Claus Henrik
Bennett, Eric Paul
Pedersen, Ole Birger
Coskun, Mehmet
Troelsen, Jesper Thorvald
CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title_full CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title_fullStr CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title_full_unstemmed CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title_short CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)
title_sort cdx2 regulates interleukin‐33 gene expression in intestinal epithelial cells (ls174t)
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167865/
https://www.ncbi.nlm.nih.gov/pubmed/33838073
http://dx.doi.org/10.1002/2211-5463.13161
work_keys_str_mv AT larsensylvester cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT seidelinjakobbenedict cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT davidsenjohanne cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT dahlgaardkatja cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT nielsenclaushenrik cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT bennettericpaul cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT pedersenolebirger cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT coskunmehmet cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t
AT troelsenjesperthorvald cdx2regulatesinterleukin33geneexpressioninintestinalepithelialcellsls174t